Hashimoto's thyroiditis was first described in 1912 by Japanese physician Hakaru Hashimoto, after whom it is named. It is a classic organ-specific autoimmune disease characterized by lymphocytic infiltration of the thyroid gland, positivity for anti-thyroid peroxidase antibodies (TPOAb) and/or anti-thyroglobulin antibodies (TgAb), and often progressive hypothyroidism. The global prevalence in adults is approximately 5–10%; it is significantly more common in women than in men, with the peak incidence occurring between ages 30 and 50. Diagnosis rates have risen in recent years in China. Typical symptoms include fatigue, cold intolerance, weight gain, goiter, depression, bloating, constipation or diarrhea, forgetfulness, anxiety, insomnia, dry skin, and hair loss. The disease progresses slowly, and most patients eventually require lifelong levothyroxine (LT4) replacement therapy. Quality of life is markedly reduced, particularly in terms of overall health and vitality, which correlate negatively with TPOAb/TgAb levels. These antibodies also correlate positively with inflammatory cytokines TNF-α and IFN-γ, suggesting that elevated antibodies exacerbate multi-system symptoms affecting digestion, endocrinology, neuropsychiatry, and skin.

Figure 1. Mechanisms contributing to the pathology of autoimmune thyroid disease (AITD)

The core pathogenic mechanism of Hashimoto's thyroiditis (HT) involves breakdown of immune tolerance, typically driven by a combination of genetic susceptibility and environmental triggers, ultimately leading to thyroid fibrosis and loss of function. The specific pathological processes and regulatory mechanisms are as follows:

1. Central role of immune cells and cytokines: Immune imbalance is the key driver—Th1/Th17 cell subset polarization triggers a cytokine storm, accompanied by increased oxidative stress that promotes follicular cell apoptosis; B lymphocytes produce autoantibodies, T lymphocytes mediate inflammatory responses, and reduced Treg cell numbers lead to loss of immune regulation; NK cells and macrophages induce apoptosis via perforin, granzymes, and serglycin, while IFN-γ and TNF-α activate the NLRC4 inflammasome to trigger pyroptosis, further amplifying inflammatory damage.
2. Tissue microenvironment features revealed by spatial transcriptomics: Damaged thyroid follicular cells (TFCs) upregulate CD74 and MIF expression, enhancing antigen presentation; the stroma is enriched with inflammatory fibroblasts (distinct from ADIRF+ myofibroblasts in Graves' disease); increased PLVAP+ fenestrated vessels promote lymphocyte infiltration and accelerate local disease progression.
3. Metabolic and epigenetic regulatory mechanisms: At the metabolic level, there are disruptions in phospholipid, eicosanoid, and carnitine metabolism, with significant enrichment in choline, glycerophospholipid, and linoleic acid pathways; at the epigenetic and signaling level, dysregulation of vitamin D receptor signaling, gut microbiota dysbiosis, mitochondrial variants, and non-coding RNAs (miRNAs regulating TSHR expression, lncRNAs affecting Th cell differentiation, and circRNAs mediating epigenetic modifications) collectively contribute to immune imbalance.

HT is a complex disease involving intertwined abnormalities across immunity, tissue microenvironment, metabolism, and epigenetics, with immune dysregulation as the central driver and multiple pathways synergistically promoting disease progression.

Figure 2. Key mechanisms leading to thyroid damage in Hashimoto's thyroiditis (HT)

Key Research Targets in Hashimoto's Thyroiditis

Key targets and downstream pathways:

• TPO/Tg antigen presentation and antibody production: Directly mediate complement-dependent cytotoxicity and apoptosis.
• Cytokine network (IFN-γ, IL-6, IL-17, IL-21, IL-22): Amplifies inflammatory cycles and activates pyroptosis.
• Oxidative stress and selenium-dependent enzymes (e.g., GPx): Selenium deficiency exacerbates free radical damage.
• Vitamin D signaling: Inhibits dendritic cell maturation, promotes Treg cells, and reduces Th17 activity.
• Microbiome and ncRNAs: Gut microbiota dysbiosis affects immune tolerance; ncRNAs (e.g., miR-155) regulate autoreactivity.

Summary of Recent Research Advances

• Selenium supplementation: A 2024 systematic review and meta-analysis showed that selenium supplementation significantly reduces TPOAb titers (independent of baseline selenium status and LT4 treatment) and improves mood/overall well-being, though effects on TSH or quality of life are limited.

• Vitamin D intervention: Multiple RCT meta-analyses indicate that vitamin D supplementation (especially >3 months or active calcitriol) significantly lowers TPOAb and TgAb titers, improves TSH, FT3/FT4 levels, and delays progression to hypothyroidism.

• Emerging directions: Antigen-specific immunotherapy (e.g., nanomaterial delivery of autoantigens to induce tolerance, mRNA vaccines targeting TSHR) shows promise in animal models, with clinical trials evaluating safety and efficacy; stem cell therapy (MSC immunomodulation), metformin as an adjunct to reduce antibodies, combined LT4+LT3 therapy for persistent symptoms, and early exploration of targeting NK cells or inflammasome pathways. Probiotic supplementation can modulate the microbiome and improve thyroid function. Research in 2025 emphasizes multi-pathway systemic regulation, such as inhibiting pro-inflammatory cytokines and stimulating anti-inflammatory cytokines (IL-10, IL-2).

These advances highlight that although HT is driven by multiple factors, single hormone replacement cannot fully reverse immune damage. Multi-pathway adjunctive interventions (e.g., selenium + vitamin D + probiotics) can lower antibodies and alleviate inflammation, offering new strategies for disease modification. High-quality recombinant proteins and antibody tools (e.g., anti-TPO, anti-Tg, vitamin D receptor-related) are essential for mechanism validation and drug screening.

abinScience Hashimoto's Thyroiditis Research Toolkit

Below are the latest abinScience recombinant proteins and antibodies related to Hashimoto's thyroiditis. Catalog numbers link directly to product pages.

Protein

Antibody

Kit